Due to advances in fetal echocardiography, fetal cardiac surgery is an increasingly viable strategy to prevent simple cardiac lesions from progressing into serious defects requiring multiple corrective surgeries after birth. A significant obstacle to successful fetal cardiac bypass is placental dysfunction; hypothesized causes include blood contact with extracorporeal surfaces, priming fluids, and increased placental vascular resistance. The overall goal of this Phase II proposal is to complete development of a novel fetal cardiac bypass circuit designed to minimize placental dysfunction by minimizing priming volume, delivering pulsatile flow, and providing adequate gas exchange when the placenta is excluded from the fetal circulation. We believe this fetal perfusion system will serve as key "enabling technology" to facilitate wider adoption of in utero cardiac surgery. The specific aims of this Phase II proposal include: 1) utilizing computational fluid dynamics (CFD) techniques to optimize and subsequently freeze the designs of the fetal blood pump and miniature oxygenator developed during our Phase I work, 2) fabricating a sufficient number of prototype pumps and oxygenators for in vitro and in vivo testing and producing final Phase II componentry using plastic injection molding, 3) moving from the LabView-based controller used in Phase I to a hardware-based stand-alone control unit capable of operating the pump in both continuous and pulsatile flow modes and containing the alarms and other functionality needed for clinical use, 4) performing in vitro testing of circuit with lamb blood to evaluate hemodynamic, gas transfer, and biocompatibility performance, and 5) performing acute and chronic in vivo testing of circuit in a pregnant ewe model. Ultimately, we anticipate that our Phase II fetal perfusion system will advance the field of in utero surgery by allowing clinicians to more safely perform fetal cardiac surgery by avoiding placental dysfunction and, as a result, reduce if not eliminate the multiple, complicated post-birth surgical corrections currently required by these patients. [unreadable] [unreadable] Project Narrative: The overall goal of this Phase II proposal is to complete development of a novel fetal cardiac bypass circuit specifically designed to mitigate placental dysfunction by minimizing priming volume, delivering pulsatile flow, and providing adequate gas exchange when the placenta is excluded from the fetal circulation. Ultimately, this Phase II fetal perfusion system will advance the field of in utero surgery by enabling clinicians to more safely perform fetal cardiac surgery by avoiding placental dysfunction and, as a result, reduce if not eliminate the multiple, complicated post-birth surgical corrections currently required by these patients. [unreadable] [unreadable] [unreadable]